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Journal Article 2012; 33(3): 279-284 PubMed PMID: 22635084 Citation  Keywords:  Animals, Catalase:metabolism, Cell Line, Tumor, Cell Proliferation:drug effects, Cell Survival:drug effects, Diabetic Neuropathies:metabolism, Glucose:pharmacology, Hyperglycemia:metabolism, Neurilemmoma:metabolism, Oxidative Stress:drug effects, Rats, Re.   

OBJECTIVES: Schwann cells may be involved in the pathogenesis of several neuropathies, such as those linked to an excess of d-glucose. Indeed, hyperglicemic condition can often result in the production of high reactive/nitrosative oxygen species concentration and possible damage of several cell structures. In the present work attention has been focused on the possible nitrosative effect of hyperglycemia on RT4 Schwannoma cell lines.

METHODS: Cells were cultured for 72hrs in the presence of 180 mM D-glucose. Morphology, growth rate, cell viability, catalase evaluation and Western blot were performed.

RESULTS: In D-glucose-exposed cells, 3-Nitrotyrosine increase and subsequent modifications in cell morphology, growth rate, viability and catalase activity were found.

CONCLUSION: Our findings suggested a possible primary role played by Schwann cells in the hyperglicemic neuropathy pathogenesis, through the excessive production of RNS and a decrease in antioxidant defense systems, bearing out the importance of the "nitrosative hypothesis" in the hyperglicemic-induced nervous system complications....

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Journal Article 2009; 30(4): 515-524 PubMed PMID: 20010498 Citation  Keywords:  Androgens:pharmacology, Animals, Catalase:metabolism, Cell Division:drug effects, Cell Line, Transformed, Cell Survival:drug effects, Down-Regulation:drug effects, Drug Interactions, Glioma, Glucose:pharmacology, Mice, Microtubules:drug effects, Neuroblas.   

OBJECTIVES: Diabetic complications can often affect the central nervous system since the chronic exposure to hyperglycemia can result in the production of high concentration of reactive oxygen species with subsequent damage of several cell structures such as the cytoskeleton. In order to antagonize the oxidative status many substances have been tested as antioxidants. In the present work attention has been focused on the possible nitrosative effect of hyperglycemia on microtubular network of neuroblastoma and glioma mortalized cell lines, testing the possible neuroprotective effect of testosterone.

METHODS: Neuroblastoma (C1300) and glioma (C6) cell lines were cultured in the presence of 300 mM (C1300) or 310 mM (C6) D-glucose, with or without 50 nM testosterone. After 72 hrs, morphology, growth rate, cell viability and catalase activity were evaluated. In addition, with the aim to detect any changes in the amount of tubulin isoforms, Western blot analysis was performed.

RESULTS: In D-glucose-exposed cells, it was found a down-regulation of tubulin isoforms and an increase in 3-nitro-L-tyrosine and subsequent modifications in cell morphology, growth rate, viability and catalase activity. All these changes were more severe in neuroblastoma than in glioma cell line. When testosterone was added to the medium, all the parameters were very similar to controls. This neuroprotective action was well-detectable in C1300 cells, whereas testosterone was not able to recover significantly in C6 cells.

CONCLUSION: Our results displayed: i) a selective action of high glucose on microtubules; ii) a different sensitivity to oxidative stress in neuronal and glial cells; iii) a different neuroprotective action of testosterone on neuronal and glial cells....

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Journal Article 2008; 29(5): 775-778 PubMed PMID: 18987578 Citation  Keywords:  Aldehyde Reductase:antagonists & inhibitors, Animals, Blotting, Western, Calcimycin:pharmacology, Cattle, Cell Line, Electrochemistry, Endothelial Cells:drug effects, Endothelium, Vascular:drug effects, Enzyme Inhibitors:pharmacology, Glucose:pharmacology.   

OBJECTIVES: An increased glucose utilization by aldose reductase (ALR-2) has been implicated in the pathogenesis of diabetic vascular complications. In this process, several mechanisms are involved, including the depletion of cofactors required for the action of antioxidant enzymes or endothelial NO synthase. In this study, the effect of a novel ALR-2 inhibitor JMC-2004 on hyperglycemia-induced endothelial dysfunction was studied.

METHODS: Bovine aortic endothelial cells (BAEC) were treated with glucose (30 mM), JMC-2004 (0.01mM), or glucose and JMC-2004 for 24 h. The cells were then stimulated with calcium ionophore A23187 after which NO production was measured electrochemically using a porphyrine-coated carbon NO electrode. Nitrite concentrations were determined in the cell supernatants. The peroxyl and hydroxyl radical-scavenging activity of JMC-2004 was measured with luminol-enhanced chemiluminescence. The expression of eNOS was determined by Western blotting. JMC-2004 IC50 for ALR-2 was determined colorimetrically with D-glyceraldehyde as a substrate.

RESULTS: Incubating the cells with 30 mM glucose strongly diminished A23187- induced NO production. Treatment with JMC-2004 restored NO production by 40% without affecting eNOS expression. This effect was probably antioxidantindependent, since JMC-2004 did not have any antioxidant capacity. JMC-2004 exerted high selectivity towards ALR-2.

CONCLUSIONS: ALR-2 inhibition with JMC-2004 was able to abolish hyperglycemia- induced endothelial dysfunction in bovine aortic endothelial cells....

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Journal Article 2007; 28(6): 854-860 PubMed PMID: 18063937 Citation  Keywords:  Animals, Antipsychotic Agents:pharmacology, Clozapine:pharmacology, Dose-Response Relationship, Drug, Glucose:pharmacology, In Vitro Techniques, Insulin:secretion, Islets of Langerhans:drug effects, Male, Rats, Rats, Wistar, Statistics, Nonparametric,.   

OBJECTIVES: Treatment with the atypical antipsychotic clozapine is frequently associated with metabolic side-effects such as weight gain, lipid abnormalities and diabetes mellitus. Since insulin is a hormone that is involved in both the regulation of body weight, as well as in lipid metabolism and glucose regulation, an effect of clozapine on insulin secretion and/or on insulin action - at least in part - might explain its capability to induce these side-effects. The aim of this study was therefore to examine the influence of clozapine on insulin release in vitro.

METHODS: The effect of clozapine in three different concentrations, 10(-6), 10(-5) and 10(-4) M, was investigated on both basal (i.e. 3.3 mM glucose) and glucose-stimulated (i.e. 16.7 mM glucose) insulin release, using isolated rat islets of Langerhans.

RESULTS: The presence of clozapine in the concentrations of 10(-6), 10(-5) and 10(4 )M significantly increased basal insulin release compared to the control after 4 h (but not after 1 h) of incubation. As regards the glucose-stimulated insulin release, the presence of clozapine in the concentrations of 10(-5) and 10(-4) M, but not in that of 10(-6) M, significantly inhibited the glucose-stimulated insulin release compared to the control after both 1 and 4 h of incubation.

CONCLUSION: This study demonstrates that the atypical antipsychotic clozapine exerts dual effects on insulin release in vitro, through stimulating basal insulin release and inhibiting glucose-stimulated insulin release. Both these effects of clozapine on insulin release may contribute to its disadvantage inducing metabolic side-effects....

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Journal Article 2005; 26(3): 205-208 PubMed PMID: 15990722 Citation  Keywords:  Animals, Antipsychotic Agents:pharmacology, Dibenzothiazepines:pharmacology, Glucose:pharmacology, Insulin:metabolism, Islets of Langerhans:drug effects, Male, Organ Culture Techniques, Piperazines:pharmacology, Quetiapine Fumarate, Rats, Rats, Wistar, Ri.   

OBJECTIVE: In the light of the recent finding that the atypical antipsychotics clozapine and olanzapine have a stimulatory effect on basal insulin release in vitro, the influence on insulin release of three other atypical agents; quetiapine, risperidone and ziprasidone, was examined.

METHODS: The effect of each atypical antipsychotic in a concentration of 10(-6) M was investigated on both basal and glucose-stimulated insulin release from isolated rat pancreatic islets.

RESULTS: No difference in effect on insulin release was found for any of the three atypical antipsychotic substances compared to controls without antipsychotics, either in basal or in glucose-stimulated insulin release.

CONCLUSION: This study demonstrates that the main compounds of quetiapine, risperidone and ziprasidone do not increase insulin release from isolated pancreatic islets, which stands in clear contrast to what has been found previously for clozapine and olanzapine. Thus, atypical antipsychotics seem to differ in their effect on insulin release in vitro....

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